Background/Objectives: Obesity is increasingly recognized as a global health concern due to its association with metabolic disorders and gut microbiota dysbiosis. While probiotics offer promise in regulating gut microbiota and improving host metabolism, strain-specific effects remain underexplored, particularly for canine-derived probiotics. This study aimed to isolate and characterize a novel probiotic strain, Ligilactobacillus animalis LA-1, and evaluate its anti-obesity effects and underlying mechanisms using a high-fat diet (HFD)-induced obese mouse model. Methods: LA-1 was isolated from the feces of a healthy dog and assessed for probiotic potential in vitro, including gastrointestinal tolerance, bile salt hydrolase activity, cholesterol-lowering capacity, and fatty acid absorption. Male C57BL/6J mice were fed either a standard chow diet or an HFD for 16 weeks, with HFD mice receiving oral LA-1 supplementation (2 × 10⁹ CFU/day). Multi-omics analyses, including 16S rRNA gene sequencing, short-chain fatty acid (SCFA) quantification, and untargeted liver metabolomics, were employed to investigate the effects of LA-1 on gut microbiota composition, metabolic pathways, and obesity-related phenotypes. Results: LA-1 supplementation significantly alleviated HFD-induced weight gain, hepatic lipid accumulation, and adipose tissue hypertrophy, without affecting food intake. It improved serum lipid profiles, reduced liver injury markers, and partially restored gut microbiota composition, decreasing the Firmicutes/Bacteroidetes ratio and enriching SCFA-producing genera. Total SCFA levels, particularly acetate, propionate, and butyrate, increased following LA-1 treatment. Liver metabolomics revealed that LA-1 modulated pathways involved in lipid and amino acid metabolism, resulting in decreased levels of acetyl-CoA, triglycerides, and bile acids. Conclusions: L. animalis LA-1 exerts anti-obesity effects via gut microbiota modulation, enhanced SCFA production, and hepatic metabolic reprogramming. These findings highlight its potential as a targeted probiotic intervention for obesity and metabolic disorders.

This research sought to assess the anti-obesity potential of Enterococcus faecalis EF-1. An extensive and robust in vitro methodology confirmed EF-1’s significant potential in combating obesity, probably due to its excellent gastrointestinal tract adaptability, cholesterol-lowering property, bile salt hydrolase activity, α-glucosidase inhibition, and fatty acid absorption ability. Moreover, EF-1 exhibited antimicrobial activity against several pathogenic strains, lacked hemolytic activity, and was sensitive to all antibiotics tested. To further investigate EF-1’s anti-obesity properties in vivo, a high-fat diet (HFD) was used to induce obesity in C57BL/6J mice. Treatment with EF-1 (2 × 10⁹ CFU/day) mitigated HFD-induced body weight gain, reduced adipose tissue weight, and preserved liver function. EF-1 also ameliorated obesity-associated microbiota imbalances, such as decreasing the Firmicutes/Bacteroidetes ratio and boosting the levels of bacteria (Faecalibacterium, Mucispirillum, Desulfovibrio, Bacteroides, and Lachnospiraceae_NK4A136_group), which are responsible for the generation of short-chain fatty acids (SCFAs). Concurrently, the levels of total SCFAs were elevated. Thus, following comprehensive safety and efficacy assessments in vitro and in vivo, our results demonstrate that E. faecalis EF-1 inhibits HFD-induced obesity through the regulation of gut microbiota and enhancing SCFA production. This strain appears to be a highly promising candidate for anti-obesity therapeutics or functional foods.

Obesity and related metabolic disorders are major global health challenges. Postbiotics, such as heat-inactivated probiotics, have attracted attention for their improved safety, stability, and potential metabolic benefits compared to live probiotics. However, the comparative anti-obesity effects and mechanisms of live versus heat-inactivated Lactiplantibacillus plantarum FRT4 remain unclear, so this study systematically evaluated their effects and mechanisms in high-fat-diet-induced obese mice. Mice received oral administration of live or heat-inactivated FRT4 (prepared by heating in a water bath at 80 °C for 5 min) for 16 weeks. Comprehensive analyses included metabolic profiling, histological evaluation, serum and liver biomarkers, gut microbiota composition, liver metabolomics, and transcriptomics. Both live and inactivated FRT4 significantly reduced body weight gain, adiposity, hepatic steatosis, and dyslipidemia, with inactivated FRT4 exhibiting comparable or superior efficacy. Notably, inactivated FRT4 restored gut microbiota composition, increased short-chain fatty acid production, and regulated hepatic metabolic pathways. Multi-omics analyses revealed modulation of lipid biosynthesis, amino acid metabolism, and energy utilization pathways. Specifically, the “biosynthesis of unsaturated fatty acids” pathway was downregulated in metabolomics and significantly enriched in transcriptomics, highlighting its central role in FRT4M-mediated metabolic reprogramming. These findings demonstrate that heat-inactivated Lp. plantarum FRT4 exerts systemic anti-obesity effects via gut–liver axis modulation, supporting its potential as a promising postbiotic intervention for obesity and metabolic dysfunction.